RT Journal Article SR Electronic T1 Over-expression Screen of Interferon-Stimulated Genes Identifies RARRES3 as a Restrictor of Toxoplasma gondii Infection JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.09.04.458998 DO 10.1101/2021.09.04.458998 A1 Rinkenberger, Nicholas A1 Abrams, Michael E. A1 Matta, Sumit K. A1 Schoggins, John W. A1 Alto, Neal M. A1 Sibley, David YR 2021 UL http://biorxiv.org/content/early/2021/09/05/2021.09.04.458998.abstract AB Toxoplasma gondii is an important human pathogen infecting an estimated 1 in 3 people worldwide. The cytokine interferon gamma (IFNγ) is induced during infection and is critical for restricting T. gondii growth in human cells. Growth restriction is presumed to be due to the induction interferon stimulated genes (ISGs) that are upregulated to protect the host from infection. Although there are hundreds of ISGs induced by IFNγ, their individual roles in restricting parasite growth in human cells remain somewhat elusive. To address this deficiency, we screened a library of 414 IFNγ induced ISGs to identify factors that impact T. gondii infection in human cells. In addition to IRF1, which likely acts through induction of numerous downstream genes, we identified RARRES3 as a single factor that restricts T. gondii infection by inducing premature egress of the parasite in multiple human cell lines. Overall, while we successfully identified a novel IFNγ induced factor restricting T. gondii infection, the limited number of ISGs capable of restricting T. gondii infection when individually expressed suggests that IFNγ mediated immunity to T. gondii infection is a complex, multifactorial process.Competing Interest StatementThe authors have declared no competing interest.